Low glycemic diet alters lipid metabolism and affects tumor growth

Lien, EC, Westermark, AM, Zhang, Y., et al. Low glycemic diet alters lipid metabolism and influences tumor growth. Nature (2021). https://doi.org/10.1038/s41586-021-04049-2

Commentary

In this study, dietary interventions can alter the levels of metabolites in the tumor microenvironment, which may influence cancer cell metabolism relative to ALTER tumor growth.

Although calorie restriction (CR) and ketone diets (KD) are often thought to limit tumor progression by decreasing blood glucose and insulin levels, we found that only CR inhibited the growth of selected tumor allografts in mice, suggesting that other mechanisms contribute to tumor growth inhibition.

The change in nutrient availability observed in CR, but not in KD, is a reduction in plasma and tumor lipid levels.

Upregulation of stearoyl CoA desaturase (SCD), which synthesizes monounsaturated fatty acids, is necessary for cancer cells to proliferate in a lipid-depleted environment, and CR impairs SCD activity in tumors, causing an imbalance of unsaturated and saturated fatty acids that slows tumor growth.

Enforcing SCD expression in cancer cells via a high-fat CR diet or increasing circulating lipid levels confers resistance to the effects of CR; in contrast, KD also impairs tumor SCD activity, but increased lipid availability by KD maintains the ratio of unsaturated to saturated fatty acids in tumors, and altering KD fat composition to increase tumor saturated fatty acid levels reduces tumor SCD activity and slows tumor growth.

These data suggest that the diet-induced discrepancy between tumor fatty acid unsaturating activity and the availability of specific fatty acid species determines whether a hypoglycemic diet impairs tumor growth, but the results are from an animal study and should be interpreted with caution.